COPD is characterized by lung injury and inflammation caused by noxious particles and gases, including those emanating from cigarette smoke and air pollution. Unfortunately, current active smokers represent the largest subset of COPD in the US and most individuals with COPD are not successful at quitting even though smoking cessation is the best option. A potential harm reduction strategy for those who will not or have not yet successfully quit, that has not been tested and has no health risk, is improvement of air quality. The indoor environment is of particular concern as patients with moderate to severe COPD spend the majority of their time in their homes. People with COPD who have higher exposure to indoor pollutants, including particulate matter (PM), second hand smoke (SHS), and nitrogen dioxide (NO2) have worse respiratory morbidity including a higher risk of exacerbations. These effects are not obscured by their smoking habit. Unfortunately, despite the clear detrimental impact of poor air quality on respiratory outcomes, regardless of smoking status, to our knowledge, there are no studied environmental interventions targeting indoor air quality to improve respiratory health of smokers, thus ignoring a potential target for harm reduction. Our group has substantial expertise in conducting trials successful at reducing harmful indoor exposures including 1) home interventions utilizing portable air cleaners with high efficiency particular air and carbon filters that significantly reduce indoor PM and NO2 concentrations, and 2) behavioral interventions including Motivational Interviewing (MI) to promote health behavior change and reduce home air nicotine levels and indoor SHS. We propose a randomized controlled intervention trial to test whether targeted reductions of multiple indoor pollutants (PM, SHS and NO2) in homes of smokers with COPD will improve respiratory outcomes. We have chosen a potent, multimodal intervention in order to maximize the opportunity to prove that there is a health benefit to active smokers with COPD from indoor air pollution reduction. After a one-month run in period in which all participants will receive smoking cessation strategies including MI and nicotine replacement therapy, participants unable to quit smoking (n=120) will have 1:1 randomization to receive either 1) multi-component environmental intervention (active air cleaners + MI intervention for SHS reduction) or 2) sham air cleaners. All participants will continue to receive smoking cessation counseling throughout the study period, including those that quit smoking during the run in period. We aim to determine whether a multi-component environmental intervention (targeting PM, SHS and NO2 reduction) will improve respiratory morbidity (i.e., symptoms, quality of life, lung function and exacerbation risk) (Specific Aim #1) and intermediate outcome measures (i.e., markers of airway and systemic inflammation and oxidative stress) (Specific Aim #2) in smokers with COPD. We anticipate that results from this study will inform clinical practice guidelines and health care policies aimed at reducing COPD morbidity and may have broader implications for indoor environmental recommendations for smokers with chronic disease. 1